Error-Oblivious Sample Preparation With Digital Microfluidic Lab-on-Chip

Abstract

Microfluidic chips are now being increasingly used for fast and cost-effective implementation of biochemical protocols. Sample preparation involves dilution and mixing of fluids in certain ratios, which are needed for most of the protocols. On a digital microfluidic biochip (DMFB), these tasks are usually automated as a sequence of droplet mix-split steps. In the most widely used (1:1) mix-split operation for DMFBs, two equal-volume droplets are mixed followed by a split operation, which, ideally, should produce two daughter-droplets of equal volume (balanced splitting). However, because of uncertain variabilities in fluidic operations, the outcome of droplet-split operations often becomes erroneous, i.e., they may cause unbalanced splitting. As a result, the concentration factor (CF) of each constituent fluid in the mixture may become erroneous during sample preparation. All traditional approaches aimed to recover from such errors deploy on-chip sensors to detect possible volumetric imbalance, and adopt either checkpointing-based rollback or roll-forward techniques. Most of them suffer from significant overhead in terms of assay-completion time, reactant-cost, and uncertainties in termination due to randomly occurring split-errors. In this paper, we propose a new approach to accurate dilution preparation on a DMFB that is oblivious to volumetric split-errors. It does not need any sensor and can handle multiple split-errors, deterministically. The proposed method is customized for each target-CF based on the criticality of split-errors in each mix-split step. Simulation experiments on various test-cases demonstrate the effectiveness of the proposed method.